Skip to main content
Log in

The Skok legacy and beyond: Molecular mechanisms of slow synaptic excitation in sympathetic ganglia

  • Lectures
  • Published:
Neurophysiology Aims and scope

Abstract

Vladimir Skok and his colleagues did much of the pioneering work on fast excitatory synaptic transmission in sympathetic ganglia and on nicotinic acetylcholine receptors that mediate fast transmission. I and my colleagues (including Alex Selyanko, one of Vladimir’s protégés) have studied the additional process of slow synaptic excitation that is mediated by the action of acetylcholine on muscarinic receptors. This results primarily from the closure of “M-channels,” a subset of voltage-gated potassium channels composed of Kv7.2 and Kv7.3 channel subunits. These channels require membrane phosphatidylinositol-4,5-bisphosphate (PIP2) for their opening, and their closure by muscarinic receptor activation is now thought to result from the reduction in PIP2 levels that follows receptor-induced PIP2 hydrolysis. The dynamics of these two forms of synaptic excitation are compared.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. V. N. Mirgorodsky and V. I. Skok, “Intracellular potentials recorded from a tonically active mammalian sympathetic ganglion,” Brain Res., 15, 570–572 (1969).

    Article  PubMed  CAS  Google Scholar 

  2. V. I. Skok and A. Y. Ivanov, “What is the ongoing activity of sympathetic neurons?” J. Auton. Nerv. Syst., 7, 263–270 (1983).

    Article  PubMed  CAS  Google Scholar 

  3. A. A. Selyanko, V. A. Derkach, and V. I. Skok, “Fast excitatory postsynaptic currents in voltage-clamped mammalian sympathetic ganglion neurons,” J. Auton. Nerv. Syst., 1, 127–137 (1979).

    Article  PubMed  CAS  Google Scholar 

  4. V. A. Derkach, A. A. Selyanko, and V. I. Skok, “Acetylcholine-induced current fluctuations and fast excitatory post-synaptic currents in rabbit sympathetic neurons,” J. Physiol., 336, 511–526 (1983).

    PubMed  CAS  Google Scholar 

  5. V. A. Derkach, R. A. North, A. A. Selyanko, and V. I. Skok, “Single channels activated by acetylcholine in rat superior cervical ganglion.” J. Physiol., 388, 141–151 (1987).

    PubMed  CAS  Google Scholar 

  6. A. A. Selyanko, V. A. Derkach, and V. I. Skok, “Voltage-dependent actions of short-chain polymethylene bistrimethylammonium compounds on sympathetic ganglion neurons,” J. Auton. Nerv. Syst., 6, 13–21 (1982).

    Article  PubMed  CAS  Google Scholar 

  7. V. I. Skok, A. A. Selyanko, and V. A. Derkach, “Channel-blocking activity is a possible mechanism for a selective ganglionic blockade,” Pflügers Arch., 398, 169–171 (1983).

    Article  PubMed  CAS  Google Scholar 

  8. M. V. Skok, L. P. Voitenko, S. V. Voitenko, et al., “Alpha subunit composition of nicotinic acetylcholine receptors in the rat autonomic ganglia neurons as determined with subunit-specific anti-alpha(181-192) peptide antibodies,” Neuroscience, 93, 1427–1436 (1999).

    Article  PubMed  CAS  Google Scholar 

  9. H. E. Purnyn, O. V. Rikhalsky, M. V. Skok, and V. I. Skok, “Functional nicotinic acetylcholine receptors in the neurons of rat intracardiac ganglia,” Fiziol. Zh., 50, No. 4, 79–84 (2004).

    PubMed  CAS  Google Scholar 

  10. N. V. Marrion, T. G. Smart, S. J. Marsh, and D. A. Brown, “Muscarinic suppression of the M-current in the rat sympathetic ganglion is mediated by receptors of the M1-subtype,” Br. J. Pharmacol., 98, 557–573 (1989).

    PubMed  CAS  Google Scholar 

  11. F. F. Weight and J. Votava, “Slow synaptic excitation in sympathetic ganglion cells: evidence for synaptic inactivation of potassium conductance,” Science, 170, 755–758 (1970).

    Article  PubMed  CAS  Google Scholar 

  12. D. A. Brown and P. R. Adams, “Muscarinic suppression of a novel voltage-sensitive K+-current in a vertebrate neuron,” Nature, 283, 673–676 (1980).

    Article  PubMed  CAS  Google Scholar 

  13. H. S. Wang and D. McKinnon, “Potassium currents in rat prevertebral and paravertebral sympathetic neurons,” J. Physiol., 485, 319–337 (1995).

    PubMed  CAS  Google Scholar 

  14. T. J. Jentsch, “Neuronal KCNQ potassium channels: physiology and role in disease,” Nat. Rev. Neurosci., 1, 21–30 (2000).

    Article  PubMed  CAS  Google Scholar 

  15. H. S. Wang, Z. Pan, W. Shi, et al., “KCNQ2 and KCNQ3 potassium channel subunits: molecular correlates of the M-channel,” Science, 282, 1890–1893 (1998).

    Article  PubMed  CAS  Google Scholar 

  16. J. K. Hadley, G. M. Passmore, L. Tatulian, et al., “Stoichiometry of expressed KCNQ2/KCNQ3 channels and subunit composition of native ganglionic M-channels deduced from block by tetraethylammonium (TEA),” J. Neurosci., 23, 5012–5019 (2003).

    PubMed  CAS  Google Scholar 

  17. A. A. Selyanko, J. K. Hadley, I. C. Wood, et al., “Inhibition of KCNQ1-4 potassium channels expressed in mammalian cells via M1_muscarinic acetylcholine receptors,” J. Physiol., 522, 349–355 (2000).

    Article  PubMed  CAS  Google Scholar 

  18. A. A. Selyanko, C. E. Stansfeld, and D. A. Brown, “Closure of potassium M-channels by muscarinic acetylcholine-receptor stimulants requires a diffusible messenger,” Proc. Roy. Soc., London, Ser B. 250, 119–125 (1992).

    Article  CAS  Google Scholar 

  19. J. E. Haley, F. C. Abogadie, P. Delmas, et al., “The alpha subunit of Gq contributes to muscarinic inhibition of the M-type potassium current in sympathetic neurons,” J. Neurosci., 18, 4521–4531 (1998).

    PubMed  CAS  Google Scholar 

  20. B. C. Suh and B. Hille, “Regulation of ion channels by phosphatidylinositol 4,5-bisphosphate,” Curr. Opin. Neurobiol., 15, 370–378 (2005).

    Article  PubMed  CAS  Google Scholar 

  21. B. C. Suh and B. Hille, “Regulation of KCNQ channels by manipulation of phosphoinositides,” J. Physiol., 528, 911–916 (2007).

    Article  Google Scholar 

  22. P. Delmas and D. A. Brown, “Pathways modulating neural KCNQ/M (Kv7) potassium channels,” Nat. Rev. Neurosci., 6, 850–62 (2005).

    Article  PubMed  CAS  Google Scholar 

  23. D. A. Brown, S. A. Hughes, S. J. Marsh, and A. Tinker, “Regulation of M (Kv7.2/7.3) channels in neurons by PIP2 and products of PIP2_hydrolysis: significance for receptor-mediated inhibition,” J. Physiol., 582, 917–925 (2007).

    Article  PubMed  CAS  Google Scholar 

  24. N. Gamper and M. S. Shapiro, “Target-specific PIP2 signalling: how might it work?” J. Physiol., 582, 967–975 (2007).

    Article  PubMed  CAS  Google Scholar 

  25. J. S. Winks, S. Hughes, A. K. Filippov, et al., “Relationship between membrane phosphatidylinositol-4,5-bisphosphate and receptor-mediated inhibition of native neuronal M channels,” J. Neurosci., 25, 3400–3413 (2005).

    Article  PubMed  CAS  Google Scholar 

  26. S. Hughes, S. J. Marsh, A. Tinker, and D. A. Brown, “PIP(2)-dependent inhibition of M-type (Kv7.2/7.3) potassium channels: direct on-line assessment of PIP(2) depletion by Gq-coupled receptors in single living neurons,” Pflügers Arch. Apr. 20 (2007) [Epub ahead of print].

  27. B. C. Suh, L. F. Horowitz, W. Hirdes, et al., “Regulation of KCNQ2/KCNQ3 current by G protein cycling: the kinetics of receptor-mediated signaling by Gq,” J. Gen. Physiol., 123, 663–683 (2004).

    Article  PubMed  CAS  Google Scholar 

  28. D. A. Brown and A. A. Selyanko, “Membrane currents underlying the slow excitatory post-synaptic potential in the rat sympathetic ganglion,” J. Physiol., 365, 335–364 (1985).

    Google Scholar 

  29. D. A. Brown, A. A. Selyanko, J. K. Hadley, and L. Tatulian, “Some pharmacological properties of neural KCNQ channels,” Neurophysiology, 34, Nos. 2/3, 91–94 (2002).

    Article  CAS  Google Scholar 

  30. D. A. Brown, N. J. Buckley, M. P. Caulfield, et al., “Coupling of muscarinic acetylcholine receptors to neural ion channels: closure of K+ channels,” in: Molecular Mechanisms of Muscarinic Acetylcholine Receptor Function, J. Wess (ed.), R. G. Landes Co., Austin, TX (1995), pp. 164–182.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to D. A. Brown.

Additional information

Neirofiziologiya/Neurophysiology, Vol. 39, Nos. 4/5, pp. 284–289, July–October, 2007.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Brown, D.A. The Skok legacy and beyond: Molecular mechanisms of slow synaptic excitation in sympathetic ganglia. Neurophysiology 39, 243–247 (2007). https://doi.org/10.1007/s11062-007-0033-6

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11062-007-0033-6

Keywords

Navigation